CN113825768A

CN113825768A - Methods for treating a subject with psoriatic arthritis

Info

Publication number: CN113825768A
Application number: CN202080029205.6A
Authority: CN
Inventors: K·W·加诺卡; A·M·劳特; A·拉加万; S-L·姚
Original assignee: Sun Pharmaceutical Industries Ltd
Current assignee: Sun Pharma Global FZE; Sun Pharmaceutical Industries Ltd
Priority date: 2019-04-15
Filing date: 2020-04-15
Publication date: 2021-12-21
Also published as: MX2021012652A; EP3956357A4; JOP20210279A1; BR112021020612A2; KR20210140780A; SG11202111056YA; US20220298233A1; WO2020212874A1; IL287213A; AU2020259375A1; MA55729A; EP3956357A1; JP2022529266A; CA3143604A1

Abstract

The present disclosure relates to the anti-IL-23 p19 antibody hum13B8-B or antigen binding fragments thereof and its use for the treatment of psoriatic arthritis.

Description

Methods for treating a subject with psoriatic arthritis

Technical Field

The present disclosure relates to the anti-IL-23 p19 antibody hum13B8-B or antigen binding fragments thereof and its use for the treatment of psoriatic arthritis. In some embodiments, the present disclosure relates to a method of treating psoriatic arthritis, wherein the treatment results in an improvement in both tender and swollen joint counts relative to a baseline value. In some embodiments, the disclosure relates to a method of determining the efficacy of an anti-IL-23 p19 antibody for treating psoriatic arthritis.

Background

Psoriasis (PsO) is a chronic inflammatory skin disorder affecting about 1% to 2% of people worldwide. Psoriatic arthritis (PsA) has been defined as a unique inflammatory arthritis associated with PsO. The exact prevalence is unknown but is estimated to vary from 0.3% to 1% of the population; the prevalence of inflammatory arthritis observed in PsO patients varies from 6% to 42%. Clinical features are usually present as facet joint and mild disease. However, with time PsA becomes polyarticular and it is a serious disease in at least 20% of patients. Gladman et al, year of rheumatism (ann. rheum. dis.)64 (supplement II): ii14-ii17 (2005). Symptoms include tenderness, pain and stiffness in and around joints, fingeritis, spondylitis, heel pain and swelling, nail discoloration (discoloration, cracking or denting), and general fatigue. Patients with PsA suffering from polyarticular disease are at risk of disease progression. In addition to clinical and radiation damage exacerbations, health-related quality of life for PsA patients is reduced. Gladman et al (2005).

Current treatment options for PsA include non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, topical therapy (skin), light therapy (skin), physical therapy, and disease-modifying antirheumatic drugs (DMARDs). There are also two types of biological agents approved for the treatment of PsA, and more recently agents targeting interleukin-12 (IL-12) and IL-23. Methotrexate (MTX) is approved by the U.S. Food and Drug Administration (FDA) for the dermatological disorder PsO, but is often used outside of the indications for PsA. Methotrexate is reported to provide symptomatic relief for some patients with multiple joint involvement and PsO, but there is little scientific evidence to support the use of methotrexate as a disease-modifying agent for PsA.

Disclosure of Invention

Provided herein is a method of treating psoriatic arthritis comprising administering to a patient in need thereof an anti-IL-23 p19 antibody hum13B8-B, wherein the patient is administered a first dose of the antibody subcutaneously at week 0, and subsequently administered a subsequent dose subcutaneously every 12 weeks; and wherein the antibody hum13B8-B comprises: (i) comprises the amino acid sequence of SEQ ID NO: 1; and (ii) a polypeptide comprising the amino acid sequence of SEQ ID NO: 2.

Also provided herein is a method of treating psoriatic arthritis comprising administering to a patient in need thereof a therapeutically effective amount of the anti-IL-23 p19 antibody hum13B8-B, wherein the treatment results in at least a 20% improvement in tender and swollen joint counts relative to baseline values; and wherein the antibody hum13B8-B comprises: (i) comprises the amino acid sequence of SEQ ID NO: 1; and (ii) a polypeptide comprising the amino acid sequence of SEQ ID NO: 2.

Also provided herein is a method of treating psoriatic arthritis comprising administering to a patient in need thereof a therapeutically effective amount of the anti-IL-23 p19 antibody hum13B8-B, wherein the treatment results in at least a 50% improvement in tender and swollen joint counts relative to baseline values; and wherein the antibody hum13B8-B comprises: (i) comprises the amino acid sequence of SEQ ID NO: 1; and (ii) a polypeptide comprising the amino acid sequence of SEQ ID NO: 2.

Also provided herein is a method of treating psoriatic arthritis comprising administering to a patient in need thereof a therapeutically effective amount of the anti-IL-23 p19 antibody hum13B8-B, wherein the treatment results in at least a 70% improvement in tender and swollen joint counts relative to baseline values; and wherein the antibody hum13B8-B comprises: (i) comprises the amino acid sequence of SEQ ID NO: 1; and (ii) a polypeptide comprising the amino acid sequence of SEQ ID NO: 2.

Also provided herein is a method of determining the efficacy of an anti-IL-23 p19 antibody for the treatment of psoriatic arthritis, comprising administering to a patient the anti-IL-23 p19 antibody hum13B8-B, wherein the patient is administered a first dose of the antibody subcutaneously at week 0, and a subsequent dose is administered subcutaneously every 12 weeks after the first dose; and wherein the antibody hum13B8-B comprises: (i) comprises the amino acid sequence of SEQ ID NO: 1; and (ii) a polypeptide comprising the amino acid sequence of SEQ ID NO: 2, and wherein at least about 40% of the ACR20 response values at week 24 or week 52 are indicative of the efficacy of the antibody.

Also provided herein is a method of determining the efficacy of an anti-IL-23 p19 antibody for the treatment of psoriatic arthritis, comprising administering to a patient the anti-IL-23 p19 antibody hum13B8-B, wherein the patient is administered a first dose of the antibody subcutaneously at week 0, and a subsequent dose is administered subcutaneously every 12 weeks after the first dose; and wherein the antibody hum13B8-B comprises: (i) comprises the amino acid sequence of SEQ ID NO: 1; and (ii) a polypeptide comprising the amino acid sequence of SEQ ID NO: 2, and wherein at least about a 20% ACR50 response value at week 24 or week 52 is indicative of the efficacy of the antibody.

Also provided herein is a method of determining the efficacy of an anti-IL-23 p19 antibody for the treatment of psoriatic arthritis, comprising administering to a patient the anti-IL-23 p19 antibody hum13B8-B, wherein the patient is administered a first dose of the antibody subcutaneously at week 0, and a subsequent dose is administered subcutaneously every 12 weeks after the first dose; and wherein the antibody hum13B8-B comprises: (i) comprises the amino acid sequence of SEQ ID NO: 1; and (ii) a polypeptide comprising the amino acid sequence of SEQ ID NO: 2, and wherein at least 10% of the ACR70 response values at week 24 or week 52 are indicative of the efficacy of the antibody.

In some embodiments, provided herein is a method of determining the efficacy of an anti-IL-23 p19 antibody for the treatment of psoriatic arthritis, comprising administering to a patient the anti-IL-23 p19 antibody hum13B8-B, wherein the patient is administered a first dose of the antibody subcutaneously at week 0, and subsequently administered a subsequent dose subcutaneously every 12 weeks; and wherein the antibody hum13B8-B comprises: (i) comprises the amino acid sequence of SEQ ID NO: 1; and (ii) a polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein at week 52, an at least 75% improvement in the psoriasis area and severity index over baseline values is indicative of the efficacy of the antibody. In some embodiments, at least 90% improvement in the psoriasis area and severity index relative to baseline values at week 52 is indicative of efficacy of the antibody. In some embodiments, 100% improvement in the psoriasis area and severity index relative to baseline values at week 52 is indicative of efficacy of the antibody.

In some embodiments, provided herein is a method of determining the efficacy of an anti-IL-23 p19 antibody for the treatment of psoriatic arthritis, comprising administering to a patient the anti-IL-23 p19 antibody hum13B8-B, wherein the patient is administered a first dose of the antibody subcutaneously at week 0, and subsequently administered a subsequent dose subcutaneously every 12 weeks; and wherein the antibody hum13B8-B comprises: (i) comprises the amino acid sequence of SEQ ID NO: 1; and (ii) a polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein a decrease in the DAS28-CRP score relative to baseline at week 52 is indicative of antibody efficacy. In some embodiments, the patient may experience a 1, 2, 3, 4, 5, 6, 7, 8, or 9 unit decrease in DAS28 score.

In some embodiments, provided herein is a method of determining the efficacy of an anti-IL-23 p19 antibody for the treatment of psoriatic arthritis, comprising administering to a patient the anti-IL-23 p19 antibody hum13B8-B, wherein the patient is administered a first dose of the antibody subcutaneously at week 0, and subsequently administered a subsequent dose subcutaneously every 12 weeks; and wherein the antibody hum13B8-B comprises: (i) comprises the amino acid sequence of SEQ ID NO: 1; and (ii) a polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein a statistically significant improvement in disease activity at week 52 as determined according to the Minimum Disease Activity (MDA) criteria is indicative of the efficacy of the antibody.

Drawings

FIG. 1 is a schematic diagram showing the study design. Abbreviations: b/l is base line; LTE is long term extension; mg ═ mg; PtGA — patient global assessment; q is each; tildra ═ tirizumab (tiltrakizumab); wk equals week.

Figure 2 shows patients' ACR20/50/70 at treatment and time points during up to week 52. Abbreviation Q4W, every 4 weeks; Q12W, every 12 weeks; TIL, tirab.

Figure 3 shows ACR20/50/70 across treatment and time points for patients up to week 24. Abbreviation PBO, placebo; Q4W, every 4 weeks; Q12W, every 12 weeks; TIL, tirab. P<0.05；

Relative to placebo.

Figure 4 shows the minimal disease activity response rate for PsA patients at various treatment and time points from baseline to week 52. Error bars represent 95% confidence intervals. Abbreviations: PsA: psoriatic arthritis; Q4W: every 4 weeks; Q12W: every 12 weeks; TIL: and (3) tirab.

FIG. 5 shows the response rates of PASI75/90/100 up to various treatment and time points during cycle 52. Calculate the response rate of patients with BSA greater than or equal to 3% at baseline. For the missing response, the p-value corresponding to the black symbol was analyzed using no-response interpolation. For the non-responsive interpolated data set, the P-value was based on the Cochran-Mantel-Haenszel test (with previous anti-TNF use and baseline weight as the stratification factor). P<0.05；

Relative to placebo. Abbreviations: BSA, body surface area; PASI, psoriasis area and severity index; Q4W, every 4 weeks; Q12W, every 12 weeks; TIL, tirab.

Fig. 6 shows DAS28-CRP response rates for different treatments and time points. Error bars represent 95% confidence intervals. Abbreviations: Q4W, every 4 weeks; Q12W, every 12 weeks; TIL, tirab.

Detailed Description

The present disclosure relates to the anti-IL-23 p19 antibody hum13B8-B or antigen binding fragments thereof and its use for the treatment of psoriatic arthritis. In some embodiments, provided herein is a method of treating psoriatic arthritis, comprising administering to a patient in need thereof an anti-IL-23 p19 antibody hum13B8-B, wherein the patient is administered a first dose of the antibody subcutaneously at week 0, and subsequently administered a subsequent dose subcutaneously every 12 weeks; and wherein the antibody hum13B8-B comprises: (i) comprises the amino acid sequence of SEQ ID NO: 1; and (ii) a polypeptide comprising the amino acid sequence of SEQ ID NO: 2.

As utilized in accordance with the present disclosure, unless otherwise specified, all technical and scientific terms are to be understood as having the same meaning as commonly understood by one of ordinary skill in the art. Unless the context dictates otherwise, singular terms shall include the plural and plural terms shall include the singular.

As used herein, the term "antibody" refers to a protein that is capable of recognizing an antigen and specifically binding to the antigen. Common or conventional mammalian antibodies comprise tetramers, which are typically composed of two pairs of identical polypeptide chains, each pair consisting of one "light chain" (typically having a molecular weight of about 25 kDa) and one "heavy" chain (typically having a molecular weight of about 50-70 kDa). As used herein, the terms "heavy chain" and "light chain" refer to any immunoglobulin polypeptide having a variable domain sequence sufficient to confer specificity to a target antigen. The amino-terminal portion of each light and heavy chain typically comprises a variable domain of about 100 to 110 or more amino acids, which is typically responsible for antigen recognition. The carboxy-terminal portion of each chain typically defines a constant domain responsible for effector function. Thus, in naturally occurring antibodies, a full-length heavy chain immunoglobulin polypeptide comprises a variable domain (V)_H) And three constant domains (C)_H1、C_H2And C and_H3) And is between C_H1And C_H2A hinge region between, wherein said V_HA domain is located at the amino terminus of the polypeptide, and said C_H3The domains are located at the carboxy-terminus, and the full-length light chain immunoglobulin polypeptide comprises a variable domain (VL) and a constant domain (Cl), wherein the VL domain is located at the amino-terminus of the polypeptide and the Cl domain is located at the carboxy-terminus.

Within full-length light and heavy chains, the variable and constant domains are typically connected by a "J" region of about 12 or more amino acids, wherein the heavy chain also comprises a "D" region of about 10 or more amino acids. The variable region of each light/heavy chain pair typically forms an antigen binding site. The variable domains of naturally occurring antibodies typically exhibit the same general structure of relatively conserved Framework Regions (FRs) joined by three hypervariable regions (also known as complementarity determining regions or CDRs). The CDRs of the two chains of each pair are typically aligned by a framework region, which may enable binding to a particular epitope. From amino-terminus to carboxy-terminus, both light and heavy chain variable domains typically comprise the domains FR1, CDR1, FR2, CDR2, FR3, CDR3 and FR 4.

As used herein, the term "antigen binding fragment" refers to a portion of an intact antibody and/or to an epitope variable domain of an intact antibody. It is known that the antigen binding function of an antibody can be performed by fragments of a full-length antibody. Examples of antibody fragments include, but are not limited to, Fab ', F (ab')2, and Fv fragments, linear antibodies, single chain antibodies, diabodies, and multispecific antibodies formed from antibody fragments.

In particular embodiments, the anti-IL-23 p19 antibody hum13B8-B is temepratumab. As used herein, the term "tirucaumab" refers to a humanized anti-IL-23 p19 monoclonal antibody, also known as SCH 900222 or MK-3222. Tirab is a high affinity (297 pmol concentration [ pM ]) humanized immunoglobulin G1/κ (IgG1/κ) antibody that specifically binds to the p19 protein of the IL-23 heterodimer, but does not bind to human IL-12(IL-12/23p40 and IL12p35 heterodimers) or human IL-12/23p 40.

In particular embodiments, the terlizumab comprises a peptide comprising the amino acid sequence of SEQ ID NO: 1 and a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2, which are disclosed in U.S. patent nos. 8,404,813 and 8,293,883, the disclosures of each of which are hereby incorporated by reference in their entirety. In other embodiments, the terlizumab, or antigen binding fragment thereof, comprises a heavy chain variable domain and a light chain variable domain, wherein the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 3-5, and wherein the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 6-8, CDR1, CDR2, and CDR3 sequences.

As used herein, the terms "subject" and "patient" are interchangeable. In some embodiments, the subject and/or patient is a mammal.

A "disorder" is any condition that would benefit from treatment with an antibody of the present disclosure. "disorder" and "condition" are used interchangeably herein and include chronic and acute disorders or diseases, including those pathological conditions that predispose a patient to the disorder.

As used herein, the terms "treatment" or "treating" refer to both therapeutic treatment and prophylactic or preventative measures. Patients in need of treatment include patients with psoriatic arthritis, as well as patients who are predisposed to or are to be prevented from psoriatic arthritis.

As used herein, the term "administering" or "administering" refers to providing, contacting, and/or delivering an antibody or fragment thereof by any suitable route to achieve a desired effect. Administration can include, but is not limited to, oral, sublingual, parenteral (e.g., intravenous, subcutaneous, intradermal, intramuscular, intraarticular, intraarterial, intrasynovial, intrasternal, intrathecal, intralesional, or intracranial injection), transdermal, topical, buccal, rectal, vaginal, nasal, ocular, via inhalation, and implant.

In some embodiments, the anti-IL-23 p19 antibody hum13B8-B or an antigen-binding fragment thereof is administered every two weeks, every four weeks, every six weeks, every eight weeks, every ten weeks, or every twelve weeks.

As used herein, the term "week 0" refers to the first day of administration of the anti-IL-23 p19 antibody hum13B8-B or antigen-binding fragment thereof.

In some embodiments, the anti-IL-23 p19 antibody hum13B8-B, or antigen-binding fragment thereof, is administered within a two week treatment period, within a four week treatment period, within a six week treatment period, within an eight week treatment period, within a twelve week treatment period, within a twenty four week treatment period, within a thirty six week treatment period, within a forty eight week treatment period, within a sixty week treatment period, within a seventy two week treatment period, or within a one year or longer treatment period.

The therapeutic dose of the anti-IL-23 p19 antibody hum13B8-B or antigen-binding fragment thereof will vary depending, in part, on the size (body weight, body surface or organ size) and condition (age and general health) of the patient. In some embodiments, one or more doses of the anti-IL-23 p19 antibody hum13B8-B or an antigen-binding fragment thereof are administered to the patient, wherein the dose is 20mg, 40mg, 60mg, 80mg, 100mg, 120mg, 140mg, 160mg, 180mg, or 200 mg. In some embodiments, the first and subsequent doses of the anti-IL-23 p19 antibody hum13B8-B or an antigen-binding fragment thereof are the same. In some embodiments, the first and subsequent doses of the anti-IL-23 p19 antibody hum13B8-B or an antigen-binding fragment thereof are different. In some embodiments, the first dose is 100 mg. In some embodiments, the first dose is 200 mg. In some embodiments, the subsequent dose is 100 mg. In some embodiments, the subsequent dose is 200 mg. In some embodiments, the first and subsequent doses are 100 mg. In some embodiments, the first and subsequent doses are 200 mg.

In some embodiments, provided herein is a method of treating psoriatic arthritis comprising administering to a patient in need thereof a therapeutically effective amount of the anti-IL-23 p19 antibody hum13B8-B, wherein the treatment results in at least a 20%, at least a 50%, or at least a 70% improvement in tender and swollen joint counts relative to baseline; and wherein the antibody hum13B8-B comprises: (i) comprises the amino acid sequence of SEQ ID NO: 1; and (ii) a polypeptide comprising the amino acid sequence of SEQ ID NO: 2.

For joint counting, five clinical patterns have been described in PsA patients: distal Interphalangeal (DIP), asymmetric oligoarticular, symmetric polyarticular, spondylitis, and destructive arthritis. The peripheral joints were evaluated for tenderness and swelling. There are no effective measures to assess the peripheral joints of PsA; the measure used was the ACR joint count originally developed for the evaluation of Rheumatoid Arthritis (RA) patients. The range of ACR joint counts was 28, 44, 68, and 78 for tenderness and 28, 44, 66, and 76 for swelling (swelling was assessed not to include hip, swelling of hip joints was not felt). The ACR joint count of 68 tender joint counts and 66 swollen joint counts included the majority of joints affected by PsA and it could be easily performed at the time of the outpatient visit. It includes temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist (the carpometacarpal and intercarpal joints are included as 1 unit), Metacarpophalangeal (MCP), Proximal Interphalangeal (PIP), DIP, hip, knee, talar, middle metatarsal (including the lower skull), metatarsophalangeal, and interphalangeal joints of the toes (the proximal and distal joints of each toe are counted as 1 unit).

The percent measure of American College of Rheumatology 20/50/70 response criteria (ACR20/50/70) for subjects was at least a 20%, 50% or 70% improvement in tender joints (68) and swollen joints (66) over baseline and a related percent improvement in three of the other five: 1) PGA of disease activity (as measured by VAS); 2) PtGA for disease activity (as measured by VAS); 3) patient pain assessment (as measured with VAS); 4) patient disability self-assessment (as measured using HAQ-DI); and 5) acute phase c-reactive protein (CRP).

C-reactive protein (CRP) or high sensitivity C-reactive protein (hsCRP) is an acute phase reactant, a protein prepared by the liver and released into the blood within hours following tissue injury, the onset of infection, or other causes of inflammation, such as autoimmune disorders. A significantly increased level was observed in active psoriatic arthritis patients and served as one of the biomarkers of psoriatic arthritis disease conditions.

Physician global assessment of disease activity (PGA) refers to an assessment in which a physician assesses the PsA status of a subject by a Visual Analog Scale (VAS). The subject is evaluated according to how the subject's current arthritis is. VAS is based on a verbal description of "very good" to "very bad".

Patient global assessment of disease activity (PtGA) refers to an assessment in which subjects assess their current global status of PsA by VAS ("consider all the ways your arthritis affects you, on average, how do you behave today?and is based on a verbal description of" very good "to" very poor ".

Patient pain assessment refers to an assessment in which subjects assess their current level of pain using VAS ("the level of pain that you are currently experiencing due to your arthritis. Subjects were then scored for their pain on a scale based on a verbal description of "no pain" to "the most severe pain possible".

Patient self assessment of disability refers to an assessment in which subjects have been assessed for their general disability over the past week using the HAQ-DI questionnaire.

In some embodiments, the methods disclosed herein result in at least a 20%, at least a 50%, or at least a 70% improvement over baseline in at least three of five parameters selected from the group consisting of: (i) physician global assessment of disease activity, (ii) patient global assessment of disease activity, (iii) patient pain assessment, (iv) patient disability self assessment, and (v) acute phase CRP.

The health assessment questionnaire-disability index (HAQ-DI) is designed to assess the normal ability of a patient using the patient's usual equipment. Patients will usually find HAQ-DI clear at a glance and need very little clarification. There are eight categories of HAQ-DI evaluation: 1) dressing and grooming, 2) getting up, 3) eating, 4) walking, 5) hygiene, 6) reaching out, 7) grasping, and 8) common daily activities. For each of these categories, patients report how difficult they are in performing two or three specific activities. The time frame for disability problems is the past week, and each problem can be scored as 0 (without any difficulty), 1 (with some difficulty), 2 (with greater difficulty), or 3 (not possible). The use of ancillary means and devices for performing these activities is also recorded. Any means or assistance will be used to get that category the lowest score of 2. The score for the disability index is the average of the eight categories of scores. If the missing categories exceed two or 25%, the scale is not scored. If there are fewer than two categories missing, then the sum of the categories is divided by the number of answer categories. Higher scores indicate higher disability.

Disease activity score 28 items C-reactive protein (DAS28-CRP) refers to a measure of disease activity assessed for 28 joints, including shoulder, elbow, wrist, MCP (1 to 5), PIP (1 to 5), and knee, with all fourteen joints assessed for each side of the body. It is a composite score derived from swelling and tenderness examination of 28 joints, global assessment of pain and global status using VAS, and blood markers of inflammation (hsCRP).

The litz finger length meter (Leeds dactylometer) is a validated tool for the assessment of dactylitis. The finger length gauge is used to measure the circumference of the base of the affected finger and compare it to the contralateral finger. LDI is a measure of this comparison and the tender score for joints thought to have dactylitis (where dactylitis is defined as a 10% difference in the ratio of the circumference of the affected finger compared to the contralateral finger) (0 ═ no tenderness, 1 ═ tenderness, 2 ═ tenderness and flinching, and 3 ═ tenderness and flinching). LEI examines tenderness at six sites: two sites on each lateral epicondyle of the humerus (left and right), the medial condyle of the femur, and the achilles tendon insertion points. For each attachment point, the proximal joint assessment was made for tenderness and soft tissue swelling, and scored 1 if present. The LEI score ranged from 0 to 6.

The Psoriasis Area and Severity Index (PASI) is a measure of mean redness, thickness and degree of scaliness of the lesion weighted by the affected area (each scored on a scale of 0-4). A 75% reduction in Psoriasis Area and Severity Index (PASI) score (PASI 75) is the current benchmark for the primary endpoint of most psoriasis clinical trials.

Minimal Disease Activity (MDA) is a measure of remission. Patients were classified as having reached MDA when 5 of 7 following criteria were met: the count of the tender joints is less than or equal to 1; the swollen joint count is less than or equal to 1; the psoriasis activity and severity index is less than or equal to 1 or the body surface area is less than or equal to 3; a patient pain Visual Analog Scale (VAS) score of less than or equal to 15; the VAS score of the overall disease activity of the patient is less than or equal to 20; a Health Assessment Questionnaire (HAQ) score of less than or equal to 0.5; and the tender attachment point is less than or equal to 1.

As used herein, the term "pharmaceutical composition" or "therapeutic composition" refers to a compound or composition that is capable of inducing a desired therapeutic effect when properly administered to a patient. One embodiment of the present disclosure provides a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of at least one antibody of the present disclosure.

As used herein, the term "pharmaceutically acceptable carrier" or "physiologically acceptable carrier" refers to one or more formulation materials suitable for accomplishing or enhancing the delivery of one or more antibodies of the present disclosure.

Pharmaceutical compositions provided comprise tirab alone or in combination with a prophylactic, therapeutic and/or pharmaceutically acceptable carrier. The pharmaceutical compositions comprising tirucallol provided herein are useful for, but not limited to, diagnosing, detecting, or monitoring a disorder, preventing, treating, managing, or ameliorating a disorder or one or more symptoms thereof, and/or studying. Formulations of pharmaceutical compositions, alone or in combination with prophylactic, therapeutic and/or pharmaceutically acceptable carriers, are known to those of skill in the art.

In some embodiments, provided herein is a method of determining the efficacy of an anti-IL-23 p19 antibody for the treatment of psoriatic arthritis, comprising administering to a patient the anti-IL-23 p19 antibody hum13B8-B, wherein the patient is administered a first dose of the antibody subcutaneously at week 0, and subsequently administered a subsequent dose subcutaneously every 12 weeks; wherein the antibody hum13B8-B comprises: (i) comprises the amino acid sequence of SEQ ID NO: 1; and (ii) a polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein at least about 40% of the ACR20 response values at week 24 or week 52 are indicative of antibody efficacy. In some embodiments, at least about 50% of the ACR20 response values at week 24 or week 52 are indicative of the efficacy of the antibody. In some embodiments, at least about 60% of the ACR20 response values at week 24 or week 52 are indicative of the efficacy of the antibody.

In some embodiments, provided herein is a method of determining the efficacy of an anti-IL-23 p19 antibody for the treatment of psoriatic arthritis, comprising administering to a patient the anti-IL-23 p19 antibody hum13B8-B, wherein the patient is administered a first dose of the antibody subcutaneously at week 0, and subsequently administered a subsequent dose subcutaneously every 12 weeks; and wherein the antibody hum13B8-B comprises: (i) comprises the amino acid sequence of SEQ ID NO: 1; and (ii) a polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein at least about 20% of the ACR50 response values at week 24 or week 52 are indicative of antibody efficacy. In some embodiments, an ACR50 response value of at least about 25% at week 24 or week 52 is indicative of the efficacy of the antibody. In some embodiments, an ACR50 response value of at least about 30% at week 24 or week 52 is indicative of the efficacy of the antibody.

In some embodiments, provided herein is a method of determining the efficacy of an anti-IL-23 p19 antibody for the treatment of psoriatic arthritis, comprising administering to a patient the anti-IL-23 p19 antibody hum13B8-B, wherein the patient is administered a first dose of the antibody subcutaneously at week 0, and subsequently administered a subsequent dose subcutaneously every 12 weeks; and wherein the antibody hum13B8-B comprises: (i) comprises the amino acid sequence of SEQ ID NO: 1; and (ii) a polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein at least about 10% of the ACR70 response values at week 24 or week 52 are indicative of antibody efficacy. In some embodiments, an ACR70 response value of at least about 12% at week 24 indicates efficacy of the antibody. In some embodiments, an ACR70 response value of at least about 15% at week 24 or week 52 is indicative of the efficacy of the antibody.

In some embodiments, provided herein is a method of determining the efficacy of an anti-IL-23 p19 antibody for the treatment of psoriatic arthritis, comprising administering to a patient the anti-IL-23 p19 antibody hum13B8-B, wherein the patient is administered a first dose of the antibody subcutaneously at week 0, and subsequently administered a subsequent dose subcutaneously every 12 weeks; and wherein the antibody hum13B8-B comprises: (i) comprises the amino acid sequence of SEQ ID NO: 1; and (ii) a polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein at week 52, an at least 75% improvement in the psoriasis area and severity index over baseline values is indicative of the efficacy of the antibody. In some embodiments, an improvement of at least 90% in the psoriasis area and severity index relative to baseline values at week 52 is indicative of the efficacy of the antibody. In some embodiments, an occurrence of 100% improvement in the psoriasis area and severity index relative to baseline values at week 52 is indicative of the efficacy of the antibody.

In some embodiments, provided herein is a method of determining the efficacy of an anti-IL-23 p19 antibody for the treatment of psoriatic arthritis, comprising administering to a patient the anti-IL-23 p19 antibody hum13B8-B, wherein the patient is administered a first dose of the antibody subcutaneously at week 0, and subsequently administered a subsequent dose subcutaneously every 12 weeks; and wherein the antibody hum13B8-B comprises: (i) comprises the amino acid sequence of SEQ ID NO: 1; and (ii) a polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein a decreased DAS28-CRP score at week 52 relative to baseline value is indicative of antibody efficacy. In some embodiments, the patient may experience a 1, 2, 3, 4, 5, 6, 7, 8, or 9 unit decrease in DAS28 score.

Examples of the invention

The following examples illustrate specific embodiments of the present disclosure and various uses thereof. They are set forth for illustrative purposes only, and should not be construed as limiting the scope of the present disclosure in any way.

Example 1: administration of tirab to arthritis in a subject with active psoriasis

1. Design of research

A randomized, double-blind, placebo-controlled, multi-dose phase 2b study was performed to evaluate the efficacy of four dose groups of temepratumab administered by subcutaneous injection in subjects with active PsA (NCT 02980692). Subjects with active PsA were randomly grouped according to 1:1:1:1:1 to receive: 200 milligrams (mg) of temepratumab administered by Subcutaneous (SC) injection every (q)4 weeks until week 52; 200mg of tirab administered subcutaneously every 12 weeks until week 52; 100mg of tirab administered subcutaneously every 12 weeks until week 52; 20mg of tikitumab administered subcutaneously at weeks 0 and 12, followed by 200mg of tizoxituzumab administered at week 24 and then every 12 weeks until week 52; or placebo administered subcutaneously at

weeks

0, 4,8, 12, 16, 20 and 24, followed by 200mg of tizoxidoside administered every 12 weeks thereafter, up to week 52. All subjects received injections every 4 weeks; subjects randomized to the 12 week active treatment group received placebo injections at

weeks

4,8, 16, 20, 28, 32, 40, and 44.

The study consisted of: screening period (day-28 to day 0); part 1, double-blind, placebo-controlled period (day 1 to week 24); part 2, double blind follow-up period (week 25 to week 52); and part 3, 20 week washout period (weeks 53 to 72). During the washout period, the subject no longer received temepratumab. Subjects who exhibited clinical response to treatment at week 24 (defined as greater than or equal to 20% improvement in swelling and tender joint count from baseline, and greater than or equal to 20% improvement in patient population assessment for disease activity [ PtGA ] from baseline) entered study part 2. Subjects who received temepratumab (100 mg every 12 weeks or [ every 4 weeks and every q12 weeks ]200mg dose groups) during part 1, who did not show a clinical response to treatment at week 24, withdrew study medication. Subjects who received either placebo or 20mg of temepritumab during part 1, who did not show a clinical response to treatment at week 24 entered part 2, and received 200mg of temepritumab every 12 weeks until week 52. Subjects in part 2 who did not obtain sufficient clinical benefit at any time after week 24 discontinued study medication.

The primary endpoint was measured as the proportion of subjects who achieved a 20% improvement in the response rate from baseline according to the american college of rheumatology response criteria (ACR20) at

weeks

24 and 52. Secondary efficacy endpoints included ACR50, ACR70 response rates, and components of ACR response; the proportion of subjects in need of adjustment for background therapy; achieving a proportion of subjects with DAS28-CRP < 3.2; a proportion of subjects who achieve a Minimum Disease Activity (MDA) criterion; changes in the Index of litzitis (Leeds Dactylitis Index, LDI) and the Index of litzier attachment point inflammation (LEI) from baseline; change in HAQ-DI from baseline; and a 75%/90%/100% improvement in Psoriasis Area and Severity Index (PASI). The PK and immunogenicity of tirucaumab and adverse events (TEAE) occurring during treatment were also evaluated.

2. Selection of study population

The population of subjects includes subjects greater than or equal to 18 years old diagnosed with PsA (classified according to the psoriatic arthritis [ CASPAR ] criteria), with symptoms present for at least 6 months, tender joint numbers greater than or equal to 3 and swollen joint numbers greater than or equal to 3 at screening and baseline.

Subjects were excluded from study participation if aspartate Aminotransferase (AST) or alanine Aminotransferase (ALT) was greater than or equal to 2 times the Upper Limit of Normal (ULN), creatinine was greater than or equal to 1.5 times ULN, serum direct bilirubin was greater than or equal to 1.5mg/dL, White Blood Cell (WBC) count was < 3.0x 103/μ L, or the rheumatoid factor test was positive.

Table 1 provides a summary of demographic characteristics of the treatments according to the selected subjects. Table 2 provides a summary of baseline disease characteristics for selected subjects. N-the number of subjects in the treatment group analysis set, N-the number of subjects in the assigned category with non-missing values. Baseline is defined as the last available value before the first dose of study drug.

Table 1: summary of full analysis set of demographic characteristics by therapy

Table 2: full analysis set of baseline disease characteristics

3. Statistical analysis

The primary efficacy analysis population is the total analysis set (FAS), which is defined as all randomly grouped subjects that have received at least 1 dose of study medication (IMP). The preliminary analysis was based on the Cochran-Mantel-Haenszel assay, using in combination with previous anti-TNF and baseline body weight as stratification factors to compare the response rate of the primary endpoint (ACR20 at weeks 24 and 52) between placebo and each corresponding active dose group. In addition, response differences and corresponding Confidence Intervals (CI) between placebo and each corresponding active dose group were estimated. For the primary endpoint (ACR20), any other subjects with early withdrawal and incomplete data at week 24 were classified as non-responders. Subjects who did not show minimal response to treatment at week 16 (defined as swelling or improvement < 10% in tender joint count from baseline) may have had their background drugs adjusted according to the maximum allowable daily dose and continued to participate in the study. Any subject requiring these adjustments is considered a non-responder in the preliminary analysis.

The analysis of the primary endpoint will be based on FAS. Sensitivity analysis was performed based on PPAS.

4. Results up to week 24

A summary of subject status at week 24 is provided in table 3. The safety analysis set consisted of all randomly grouped subjects who received at least 1 dose of IMP. The full analysis set consisted of all randomized cohort subjects who received at least 1 dose of investigational drug (IMP). The compliance protocol analysis set consists of all subjects in the full analysis set without any significant protocol bias that could affect the validity of the primary efficacy variable data. The percentages are based on the number of randomly grouped subjects except for completer and abort, where the percentages are based on the number of subjects in the safety analysis set. Part 1 is a double-blind placebo-controlled period from baseline to week 24, and part 2 is a double-blind follow-up period from week 25 to week 52.

Table 3: subjects status at week 24

Table 4 shows the Cochran-Mantel Haenszel (CMH) analysis of the response rate of ACR20 up to week 24. ACR20 was calculated as the 20% improvement from baseline in tender and swollen joint counts and the 20% improvement from baseline in three of the five remaining ACR core set metrics (patient and physician global assessment, pain, disability, and acute phase CRP). Subjects receiving a temepratumab (100 mg or 200mg per 12 weeks [ 4 and 12 weeks ] dose group every 12 weeks, subjects showing no clinical response to treatment at week 24 withheld study drug and entered clearance phase according to protocol. subjects who withheld study drug were recorded at week 52/EOT week 24 assessment. bilateral 95% CI and p values are based on CMH test with previous anti-TNF use and baseline body weight as stratification factors if Mantel-Fleiss criteria were less than 5, pairwise comparisons were made based on her Fisher exact test after the stratification factor level collapsed

Continuously for

Table 5 shows the CMH analysis of ACR50 response rates up to week 24. ACR50 was calculated as 50% improvement in tender and swollen joint counts versus baseline > and 50% improvement in three of the five remaining ACR core set metrics (patient and physician global assessment, pain, disability, and acute phase CRP). The ACR50 analysis was performed in the same manner as described above for the ACR20 analysis.

Subjects receiving temepratumab (100 mg or 200mg per 12 weeks [ every 4 and 12 weeks ] dose groups, who showed no clinical response to treatment at week 24, withdrew study drug and entered the washout period according to the protocol. subjects who withdrew study drug were recorded at week 52/EOT, week 24 assessments these assessments will be reported as part of the week 24 visit.the bilateral 95% CI and p values are based on CMH tests with previous anti-TNF use and baseline body weight as stratification factors.

Table 5: CMH analysis of ACR50 response rates (absence response-no response) -full analysis set up to week 24

Continuously for

Table 6 shows the CMH analysis of ACR70 response rates up to 24 weeks. ACR70 was calculated as 70% improvement from baseline in tender and swollen joint counts and 70% improvement from baseline in three of the five remaining ACR core set metrics (patient and physician global assessment, pain, disability, and acute phase CRP). The ACR70 analysis was performed in the same manner as described above for the ACR20 analysis.

Table 6: CMH analysis of ACR70 response rates up to week 24 (absence response-no response) -full analysis set

Continuously for

4. Results up to week 52

Of the 500 patients screened, 391 were randomly grouped and received ≧ 1 dose of drug. The proportion of ACR20/50/70 responders using temab was better than placebo by week 24; after week 24, until week 52, responders of temepratumab 20 → 200mg Q12W and placebo → 200mg Q12W further increased (fig. 2 and fig. 3). Other efficacy results are shown in table 7.

MDA was evaluated throughout the study and MDA response was achieved when 5 of 7 criteria were met. Baseline disease characteristics associated with MDA varied little between study groups (table 8). By week 24, MDA status was achieved in significantly more placebo patients receiving temepratumab (0% to 24% -39% versus 0% to 7%; p <0.02 for all groups); as the treatment continued with temepratumab, the proportion further increased (45% -64%) until week 52, including those patients who switched from placebo to temepratumab (47%) (fig. 4).

At week 24, temab treatment significantly increased the proportion of PASI75/90/100 responders relative to placebo; the ratio then continued to increase and remained stable until week 52 (fig. 5). Similarly, after week 24, PASI75/90/100 response increased to week 36 and remained stable to week 52 in patients who transitioned from placebo to temepratumab 200mg Q12W or escalated from temepratumab 20 to 200mg Q12W. In terms of skin response, a significant improvement in PASI75 of temepratumab 200mg Q12W occurred as early as week 4 relative to placebo. Until week 52, temepritumab had an acceptable safety profile.

DAS28-CRP has been shown to be reliable for PsA, and patients reaching a score <3.2 are considered responders. At baseline, disease characteristics were consistent between treatment groups, and DAS28-CRP scores <3.2 in 1.3% -7.7% of patients (table 9). At week 24, DAS28-CRP response rates were increased for all the temepratumab treatment groups relative to placebo (fig. 6). After week 24, response rates continued to increase and were maintained until week 52, including patients who switched from placebo to temepratumab.

Overall, 50.4%/39.9% and 2.3%/1.0% of patients experienced TEAE and severe AE, respectively, from baseline → week 24/week 25 → week 52. The most frequent TEAEs were nasopharyngitis (combined temab group 5.4%/4.2% versus placebo 6.3%/3.8%) and upper respiratory infections (combined temab group 3.8%/4.2% versus placebo 1.3%/0.0%). One patient (0.3%) stopped taking medication due to hypertension before week 24. From baseline → week 24, the TIL100mg Q12W group reported 1 pyelonephritis and urinary tract infection, and the TIL 20mg → 200mg Q12W group reported 1 chronic tonsillitis. During week 25 → week 52, TIL 20mg → 200mg Q12W group reported 1 malignancy. No death or major cardiac adverse events occurred.

TABLE 7 clinical efficacy at week 52 (W52)

^aBaseline average.^bMean change from baseline.

Table 8: baseline disease characteristics associated with minimal disease activity at week 52

Data are reported as mean values.

Total number of patients analyzed (n) was 76, 79, 76, 78, respectively.

The total number of patients analyzed (n) was 75, 79, 76, 75, respectively.

TABLE 9 Baseline disease characteristics associated with DAS28-CRP

Unless otherwise stated, data are reported as mean ± standard deviation.

Total number of pts analyzed (n) 71, 69, 70, 68, 62.

ES, erythrocyte sedimentation rate; hsCRP, high sensitivity C-reactive protein; PBO, placebo; PtGA, patient global assessment; pts, patient; Q4W, every 4 weeks; Q12W, every 12 weeks; TIL, tirab.

5. And (4) conclusion:

tirucalizumab showed surprisingly high efficacy in this clinical trial with a Q12Wk dosing regimen. When treating joint manifestations of active psoriatic arthritis, the efficacy of temab was found to be significantly greater than placebo as measured according to ACR20, ACR50, and ACR70 response criteria. While the present disclosure has been described in terms of various embodiments, it is to be understood that variations and modifications will occur to those skilled in the art. It is, therefore, intended that the appended claims cover all such equivalent variations as fall within the scope of the disclosure as claimed. In addition, the section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

Each embodiment described herein can be combined with any other embodiment unless explicitly indicated to the contrary. In particular, any feature or embodiment indicated as preferred or advantageous may be combined with any other feature or features or embodiment or embodiments indicated as preferred or advantageous unless clearly indicated to the contrary.

Claims

1. A method of treating psoriatic arthritis comprising administering to a patient in need thereof an anti-IL-23 p19 antibody hum13B8-B, wherein the patient is administered a first dose of the antibody subcutaneously at week 0, and subsequently administered a subsequent dose subcutaneously every 12 weeks; and wherein the antibody hum13B8-B comprises:

(i) comprises the amino acid sequence of SEQ ID NO: 1; and

(ii) comprises the amino acid sequence of SEQ ID NO: 2.

2. The method of claim 1, wherein the first dose and the subsequent dose are the same.

3. The method of claim 1, wherein the first dose and the subsequent dose are different.

4. The method of claim 1, wherein the first dose is 100 mg.

5. The method of claim 1, wherein the first dose is 200 mg.

6. The method of claim 1, wherein the subsequent dose is 100 mg.

7. The method of claim 1, wherein the subsequent dose is 200 mg.

8. The method of claim 2, wherein the first and subsequent doses are 100 mg.

9. The method of claim 2, wherein the first and subsequent doses are 200 mg.

10. The method of claim 3, wherein the first dose is 100mg and the subsequent dose is 200 mg.

11. The method of claim 3, wherein the first dose is 200mg and the subsequent dose is 100 mg.

12. The method of claim 1, wherein the treatment comprises administering the subsequent dose every 12 weeks for at least up to 24 weeks.

13. The method of claim 1, wherein the treatment comprises administering the subsequent dose every 12 weeks for at least up to 36 weeks.

14. The method of claim 1, wherein the treatment comprises administering the subsequent dose every 12 weeks for at least up to 48 weeks.

15. The method of claim 1, wherein the treatment comprises administering the subsequent dose every 12 weeks for at least up to 60 weeks.

16. The method of claim 1, wherein the treatment comprises administering the subsequent dose every 12 weeks for at least as long as 72 weeks.

17. A method of treating psoriatic arthritis, comprising administering to a patient in need thereof a therapeutically effective amount of an anti-IL-23 p19 antibody hum13B8-B, wherein the treatment results in at least a 20% improvement in tender and swollen joint counts relative to baseline; and wherein the antibody hum13B8-B comprises:

(i) comprises the amino acid sequence of SEQ ID NO: 1; and

(ii) comprises the amino acid sequence of SEQ ID NO: 2.

18. The method of claim 17, wherein the treatment further results in at least a 20% improvement relative to baseline in at least three of five parameters selected from the group consisting of: (i) physician global assessment of disease activity, (ii) patient global assessment of disease activity, (iii) patient pain assessment, (iv) patient disability self assessment, and (v) acute phase CRP.

19. A method of treating psoriatic arthritis, comprising administering to a patient in need thereof a therapeutically effective amount of an anti-IL-23 p19 antibody hum13B8-B, wherein the treatment results in at least a 50% improvement in tender and swollen joint counts relative to baseline; and wherein the antibody hum13B8-B comprises:

(i) comprises the amino acid sequence of SEQ ID NO: 1; and

(ii) comprises the amino acid sequence of SEQ ID NO: 2.

20. The method of claim 19, wherein the treatment further results in at least a 50% improvement relative to baseline in at least three of five parameters selected from the group consisting of: (i) physician global assessment of disease activity, (ii) patient global assessment of disease activity, (iii) patient pain assessment, (iv) patient disability self assessment, and (v) acute phase CRP.

21. A method of treating psoriatic arthritis, comprising administering to a patient in need thereof a therapeutically effective amount of an anti-IL-23 p19 antibody hum13B8-B, wherein the treatment results in at least a 70% improvement in tender and swollen joint counts relative to baseline; and wherein the antibody hum13B8-B comprises:

(i) comprises the amino acid sequence of SEQ ID NO: 1; and

(ii) comprises the amino acid sequence of SEQ ID NO: 2.

22. The method of claim 21, wherein the treatment further results in at least a 70% improvement from baseline in at least three of five parameters selected from the group consisting of: (i) physician global assessment of disease activity, (ii) patient global assessment of disease activity, (iii) patient pain assessment, (iv) patient disability self assessment, and (v) acute phase CRP.

23. A method of determining the efficacy of an anti-IL-23 p19 antibody for treating psoriatic arthritis, the method comprising administering to a patient the anti-IL-23 p19 antibody hum13B8-B, wherein the patient is administered a first dose of the antibody subcutaneously at week 0 and a subsequent dose is administered subcutaneously every 12 weeks after the first dose; and wherein the antibody hum13B8-B comprises:

(i) comprises the amino acid sequence of SEQ ID NO: 1; and

(ii) comprises the amino acid sequence of SEQ ID NO: 2;

and wherein an ACR20 response value of at least about 40% at week 24 or 52 is indicative of the efficacy of the antibody.

24. The method of claim 23, wherein an ACR20 response value of at least about 50% at week 24 or 52 is indicative of the efficacy of the antibody.

25. The method of claim 23, wherein an ACR20 response value of at least about 60% at week 24 or 52 is indicative of the efficacy of the antibody.

26. A method of determining the efficacy of an anti-IL-23 p19 antibody for treating psoriatic arthritis, the method comprising administering to a patient the anti-IL-23 p19 antibody hum13B8-B, wherein the patient is administered a first dose of the antibody subcutaneously at week 0 and a subsequent dose is administered subcutaneously every 12 weeks after the first dose; and wherein the antibody hum13B8-B comprises:

(i) comprises the amino acid sequence of SEQ ID NO: 1; and

(ii) comprises the amino acid sequence of SEQ ID NO: 2; and wherein an ACR50 response value of at least about 20% at week 24 or 52 is indicative of the efficacy of the antibody.

27. The method of claim 26, wherein an ACR50 response value of at least about 25% at week 24 or week 52 is indicative of the efficacy of the antibody.

28. The method of claim 26, wherein an ACR50 response value of at least about 30% at week 24 or week 52 is indicative of the efficacy of the antibody.

29. A method of determining the efficacy of an anti-IL-23 p19 antibody for treating psoriatic arthritis, the method comprising administering to a patient the anti-IL-23 p19 antibody hum13B8-B, wherein the patient is administered a first dose of the antibody subcutaneously at week 0 and a subsequent dose is administered subcutaneously every 12 weeks after the first dose; and wherein the antibody hum13B8-B comprises:

(i) comprises the amino acid sequence of SEQ ID NO: 1; and

(ii) comprises the amino acid sequence of SEQ ID NO: 2;

and wherein an ACR70 response value of at least 10% at week 24 or 52 indicates the efficacy of the antibody.

30. The method of claim 29, wherein an ACR50 response value of at least about 12% at week 24 or week 52 is indicative of the efficacy of the antibody.

31. The method of claim 29, wherein an ACR50 response value of at least about 15% at week 24 or week 52 is indicative of the efficacy of the antibody.

32. The method of any one of claims 23 to 31, wherein the first dose and the subsequent dose are the same.

33. The method of any one of claims 23 to 31, wherein the first dose and the subsequent dose are different.

34. The method of any one of claims 23-31, wherein the first dose is 100 mg.

35. The method of any one of claims 23-31, wherein the first dose is 200 mg.

36. The method of any one of claims 23 to 31, wherein the subsequent dose is 100 mg.

37. The method of any one of claims 23 to 31, wherein the subsequent dose is 200 mg.

38. The method of any one of claims 23 to 31, wherein the first and subsequent doses are 100 mg.

39. The method of any one of claims 23 to 31, wherein the first and subsequent doses are 200 mg.

40. A method of determining the efficacy of an anti-IL-23 p19 antibody for the treatment of psoriatic arthritis, the method comprising administering to a patient the anti-IL-23 p19 antibody hum13B8-B, wherein the patient is administered a first dose of the antibody subcutaneously at week 0, and subsequently administered a subsequent dose subcutaneously every 12 weeks; and wherein the antibody hum13B8-B comprises:

(i) comprises the amino acid sequence of SEQ ID NO: 1; and (ii) a polypeptide comprising the amino acid sequence of SEQ ID NO: 2;

and wherein an at least 75% improvement in the psoriasis area and severity index relative to baseline values at week 52 is indicative of the efficacy of the antibody.

41. The method of claim 40, wherein an at least 90% improvement in psoriatic area and severity index relative to baseline values at week 52 is indicative of the efficacy of the antibody.

42. The method of claim 40, wherein an at least 100% improvement in psoriatic area and severity index relative to baseline values at week 52 is indicative of the efficacy of the antibody.

43. A method of determining the efficacy of an anti-IL-23 p19 antibody for the treatment of psoriatic arthritis, the method comprising administering to a patient the anti-IL-23 p19 antibody hum13B8-B, wherein the patient is administered a first dose of the antibody subcutaneously at week 0, and subsequently administered a subsequent dose subcutaneously every 12 weeks; and wherein the antibody hum13B8-B comprises:

(i) comprises the amino acid sequence of SEQ ID NO: 1; and (ii) a polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and is

Wherein a decreased DAS28-CRP score at week 52 relative to baseline value is indicative of the efficacy of the antibody.

44. A method of determining the efficacy of an anti-IL-23 p19 antibody for the treatment of psoriatic arthritis, the method comprising administering to a patient the anti-IL-23 p19 antibody hum13B8-B, wherein the patient is administered a first dose of the antibody subcutaneously at week 0, and subsequently administered a subsequent dose subcutaneously every 12 weeks; and wherein the antibody hum13B8-B comprises:

Wherein a statistically significant improvement in disease activity at week 52 as determined by the Minimum Disease Activity (MDA) criteria is indicative of the efficacy of the antibody.